Background Naegleria fowleri is a climate-sensitive, thermophilic ameba found in warm, freshwater lakes and rivers. Primary amebic meningoencephalitis (PAM), which is almost universally fatal, occurs when N. fowleri–containing water enters the nose, typically during swimming, and N. fowleri migrates to the brain via the olfactory nerve. In August 2013, a 4-year-old child died of meningoencephalitis of unknown etiology in a Louisiana hospital. Methods Clinical and environmental testing and a case investigation were initiated to determine the cause of death and to identify potential exposures. Results Based on testing of CSF and brain specimens, the child was diagnosed with PAM. His only reported water exposure was tap water; in particular, tap water that was used to supply water to a lawn water slide on which the child had played extensively prior to becoming ill. Water samples were collected from both the home and the water distribution system that supplied the home and tested; N. fowleri were identified in water samples from both the home and the water distribution system. Conclusions This case is the first reported PAM death associated with culturable N. fowleri in tap water from a U.S. treated drinking water system. This case occurred in the context of an expanding geographic range for PAM beyond southern tier states with recent case reports from Minnesota, Kansas, and Indiana. This case also highlights the role of adequate disinfection throughout drinking water distribution systems and the importance of maintaining vigilance when operating drinking water systems using source waters with elevated temperatures.
The specific cell surface markers on mesenchymal stem/progenitor cells (MSCs) have been poorly defined in vivo, but in one recent study, an MSC subpopulation was directly isolated from a CD271-positive fraction of human bone marrow cells. The aim of this study was to identify circulating CD271(+) MSCs in human peripheral blood and investigate whether the cells are mobilized after acute myocardial infarction (MI). A flow cytometric analysis identified CD45(low/-)CD34(+)CD271(+) cells in adult human peripheral blood. The numbers of circulating CD45(low/-)CD34(+)CD133(+) cells (hematopoietic linage progenitors) were significantly lower in elderly subjects without coronary artery disease than in healthy young subjects, whereas the numbers of CD45(low/-)CD34(+)CD271(+) cells were comparable between elderly subjects and younger subjects. The CD45(low/-)CD34(+)CD271(+) and CD133(+) cell counts were both higher in patients with acute MI than in patients with stable coronary artery disease. In our investigation of the time course changes after acute MI, the CD45(low/-)CD34(+)CD133(+) cell counts gradually increased up to day 7. Over the same period, the CD45(low/-)CD34(+)CD271(+) cell counts peaked at day 3 and then declined up to day 7. Importantly, the CD271(+) cell counts at day 3 were positively correlated with the peak concentrations of creatine kinase after acute MI. Results of the present study suggest that the CD271(+) MSCs are mobilized differently from the CD133(+) hematopoietic progenitors and may play a specific role in the tissue repair process during age-related changes and after acute myocardial infarction.
Transplantation of culture-expanded adult stem/progenitor cells often results in poor cellular engraftment, survival, and migration into sites of tissue injury. Mesenchymal cells including fibroblasts and stromal cells secrete factors that protect injured tissues, promote tissue repair, and support many types of stem/progenitor cells in culture. We hypothesized that secreted factors in conditioned medium (CdM) from adult bone marrow-derived multipotent stromal cells (MSCs) could be used to prime adult cardiac stem/progenitor cells (CSCs/CPCs) and improve graft success after myocardial infarction (MI). Incubation of adult rat CPCs in CdM from human MSCs isolated by plastic adherence or by magnetic sorting against CD271 (a.k.a., p75 low-affinity nerve growth factor receptor; p75MSCs) induced phosphorylation of STAT3 and Akt in CPCs, supporting their proliferation under normoxic conditions and survival under hypoxic conditions (1% oxygen). Priming CSCs with 30x p75MSC CdM for 30 min prior to transplantation into sub-epicardial tissue 1 day after MI markedly increased engraftment compared with vehicle priming. Screening CdM with neutralizing/blocking antibodies identified Connective Tissue Growth Factor (CTGF) and Insulin as key factors in p75MSC CdM that protected CPCs. Human CTGF peptide (CTGF-D4) and Insulin synergistically promoted CPC survival during hypoxia in culture. Similar to CdM priming, priming of CSCs with CTGF-D4 and Insulin for 30 min prior to transplantation promoted robust engraftment, survival and migration of CSC derivatives at 1 week and 1 month after MI. Our results indicate that short-term priming of human CSCs with CTGF-D4 and Insulin may improve graft success and cardiac regeneration in patients with MI.
The patient was treated under the assumption that penetrating foreign objects in continuity with the cerebrospinal fluid space and the outside environment should be removed as soon as possible. The patient was provided appropriate antibiotics to treat potential infection of normal pharyngeal flora and organisms unique to the marine environment. The patient recovered and did not experience any residual neurological deficit.
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